title: Angiotensin-[1-12] interacts with angiotensin type I receptors.
abstract: Angiotensin-(1-12) [Ang-(1-12)], a newer member of angiotensin peptides, is proposed to be converted enzymatically to angiotensin I (Ang I) and to angiotensin II (Ang II); the latter being the bioactive peptide. We studied the Ang-(1-12) and Ang II responses in COS-7 cells or CHO cells transfected with 5 μg AT1R by monitoring [Ca(2+)]i using the Fluo-4. Ang II (1 pM-1 μM) and Ang-(1-12) (5 pM-5 μM) increased [Ca(2+)]i with an EC50 of 0.19 nM and 24 nM in COS-7 cells; and 0.65 nM and 28.7 nM in CHO cells. The AT1R antagonist losartan (1 nM-10 μM) suppressed [Ca(2+)]i induced by Ang-(1-12) and Ang II. In CHO cells transfected with 5 μg AT2R, Ang II (1 pM-1 μM) increased [Ca(2+)]i, with an EC50 of 9.68 nM; whereas, Ang-(1-12) (5 pM-5 μM) failed to elicit a significant change in [Ca(2+)]i. In CHO cells transfected with AT1R, Ang-(1-12) stimulated ERK phosphorylation with a potency 300-fold less than that of Ang II. To evaluate the activity of Ang-(1-12) on native AT1R, whole cell patch recordings were made from neurons in the rat hypothalamic slices. Ang II or Ang-(1-12) ejected by pressure from a micropipette elicited a membrane depolarization; the latter was blocked by losartan (10 μM), and not affected by the AT2R antagonist PD123319 (10 μM), nor by the angiotensin converting enzyme inhibitor captopril (10 μM). Our result shows that Ang-(1-12) may produce its biological activity by acting directly on AT1R, albeit at a concentration higher than that of Ang II.
authors.affiliation: Division of Life Science and Biotechnology Research Institute, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: King H
authors.initials: KH
authors.lastname: Chan
authors.affiliation: Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.
authors.forename: Yi H
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, 3420 N. Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Life Science and Biotechnology Research Institute, Clear Water Bay, Kowloon, Hong Kong; State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Yung H
authors.initials: YH
authors.lastname: Wong
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, 3420 N. Broad Street, Philadelphia, PA 19140, USA. Electronic address: ndun@temple.edu.
authors.forename: Nae J
authors.initials: NJ
authors.lastname: Dun
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000808:Angiotensinogen / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D016466:CHO Cells; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; C515557:proangiotensin-12, rat; D000808:Angiotensinogen; D000804:Angiotensin II; D000803:Angiotensin I; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ACE inhibitor; Angiotensin II; G-protein; Hypothalamus